Non-invasive brain stimulation approaches such as transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) can be used for two purposes, each with wide application in fundamental visual neuroscience and in visual rehabilitation. In the first of these, stimulation is used to manipulate activity in cortical networks with the goal understanding the causal role of the targeted network in generating brain responses and in perception/behavior. In the second, stimulation is used in a neuromodulatory role to induce plastic remodeling of cortical networks, either on a short-term or long-term basis. The focus of this proposal is the development of new experimental systems for combining visual and electrical stimulation that will achieve these goals. The central hypothesis of this research is that Transcranial Alternating Current Stimulation (TACS), a variant of TES, acts via constructive or destructive summation of the TACS field with the intracellular membrane potential of polarizable neurons. This hypothesis and the related hypothesis that short-term persistent effects of TACS will be proportional to the effects measured online will be tested using a combination of Functional Magnetic Resonance Imaging (FMRI), Steady-State Visual Evoked Potentials (SSVEPs) and perceptual reports. The rationale for the central hypothesis is based on several observations: first, periodic visual stimulation generates visual responses (SSVEPs) that are directly and precisely related to the stimulus frequency. Second, because TACS is also periodic and extremely narrowband, it should be possible to directly target the periodic visual response itself via summation of synaptic and electrical potentials within task-active neurons. Finally, because prior work has suggested that externally applied electric fields primarily modulate elongated neurons, the effects of TACs are predicted to depend on both the orientation of the cortical tissue and the direction of the applied TACS field. This central hypothesis will be tested in Aim 1 by determining whether BOLD responses to visual contrast depend on the relative phase of TACS and visual stimulation and the relative orientations of the cortical surface and the applied field. Aim 2 will test the hypothesis using the SSVEP and perceptual reports during binocular rivalry and binocular slant discrimination tasks. Aim 1 will also use FMRI to determine if TACS effects persist after the stimulation is turned off and if so, whether the TACS effect depends on the relative phase of visual and electrical stimulation as would be expected if the central hypothesis is correct. The experiments of this proposal will determine whether two of the main hypothesized mechanisms for TACS effectiveness derived from animal experimental models can be identified and brought under experimental control in human. They will also determine if TACS results in a short- term persistent effect on visual responsiveness. The new experimental approaches developed in this proposal have the potential for wide application in visual neuroscience and ophthalmology via their possible ability to exert causal control over neural activity and to elicit plastic changes in complex visual networks.